The mammalian olfactory system has a dual function. On the one hand it mediates the detection and discrimination of a vast number of structurally diverse odorants that are perceived as having different odors. On the other, it mediates the detection of pheromones, chemicals released from animals that stimulate neuroendocrine alterations and stereotyped behaviors in members of the same species. In most mammals, olfactory ligands are sensed at two, functionally distinct sites: the nasal olfactory epithelium (OE), which detects odorants, and the vomeronasal organ (VNO), which is thought to be specialized to detect pheromones. The VNO has been implicated in a variety of pheromone effects in rodents, including stereotyped aggressive and mating behaviors, inhibitory and stimulatory effects on estrus cycle and the onset of puberty, and "pregnancy block," a pheromone effect that appears to involve chemical individuality cues that distinguish mice of different strains. Urine appears to be a source of many of these effects. However, very few pheromones have been chemically identified, and the mechanisms by which they are detected are not yet known. Three families of sensory receptors have been identified in the olfactory system: one family of about1000 odorant receptors (ORs), expressed in the OE, and two smaller families of receptors in the VNO, the V1Rs and V2Rs, with about35 and about140 members, respectively. All three families have characteristic features of G protein coupled receptors, and members of all three families are diverse, suggesting that each family detects a variety of ligands. The presence of two large families of receptors in the VNO raises a number of questions. One is why there are two distinct families of VNO receptors. Another is why there are so many. Does one family recognize pheromones, and the other individuality cues? Do the two families detect pheromones that elicit different effects? Are some V1Rs and V2Rs expressed in only males or females? The major aim of this proposal is to gain insight into the mechanisms underlying pheromone detection by characterizing the composition and structure of the mouse V1R and V2R gene families, their expression in the VNO of male, female and neonatal animals, and their ligand recognition properties.